Differential expression and activity of P-glycoprotein and multidrug resistance-associated protein in CD34-positive KG1a leukemic cells.
CD34+ acute myeloid leukemias generally respond poorly to chemotherapy when compared to CD34- myeloid leukemias. In order to contribute to the analysis of the mechanisms involved in this drug resistance, expression and activity of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP), two drug efflux pumps conferring multidrug resistance, have been investigated in the CD34+ KG1a leukemic myeloid cell line and in two CD34- K562 and HL60 leukemic myeloid cell lines. Reverse transcription-polymerase chain reaction and dye efflux assays revealed that KG1a cells express P-gp but not MRP whereas neither P-gp nor MRP were detected in K562 and HL60 cells. In addition, KG1a cells were demonstrated to display resistance to anticancer drug substrates for P-gp such as vincristine and daunorubicin and to poorly accumulate vincristine. These results indicated that P-gp, in contrast to MRP, is expressed and functional in the drug-resistant CD34+ KG1a cell line, that may constitute a useful cellular model to analyze the constitutive chemoresistance of CD34+ acute myeloid leukemias.
Fardel
O
O
Laboratoire de Physiologie et Hematologie et INSERM U456, Faculte des Sciences Pharmaceutiques et Biologiques, 2 Avenue du Pr. L on Bernard, Rennes Cedex, 35043, France.
Payen
L
L
Courtois
A
A
Drenou
B
B
Fauchet
R
R
Rault
B
B
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000502:physiology; D018952:Antigens, CD34; D002455:Cell Division / Q000187:drug effects; D003630:Daunorubicin / Q000494:pharmacology* / Q000627:therapeutic use; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020014:K562 Cells / Q000187:drug effects / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014750:Vincristine / Q000494:pharmacology* / Q000627:therapeutic use
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D020410:Activated-Leukocyte Cell Adhesion Molecule; D018952:Antigens, CD34; D003630:Daunorubicin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D014750:Vincristine